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Global mistranslation increases cell survival under stress in Escherichia coli


Autoři: Laasya Samhita aff001;  Parth K. Raval aff001;  Deepa Agashe aff001
Působiště autorů: National Centre for Biological Sciences, Tata Institute of Fundamental research, Bangalore, India aff001
Vyšlo v časopise: Global mistranslation increases cell survival under stress in Escherichia coli. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008654
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008654

Souhrn

Mistranslation is typically deleterious for cells, although specific mistranslated proteins can confer a short-term benefit in a particular environment. However, given its large overall cost, the prevalence of high global mistranslation rates remains puzzling. Altering basal mistranslation levels of Escherichia coli in several ways, we show that generalized mistranslation enhances early survival under DNA damage, by rapidly activating the SOS response. Mistranslating cells maintain larger populations after exposure to DNA damage, and thus have a higher probability of sampling critical beneficial mutations. Both basal and artificially increased mistranslation increase the number of cells that are phenotypically tolerant and genetically resistant under DNA damage; they also enhance survival at high temperature. In contrast, decreasing the normal basal mistranslation rate reduces cell survival. This wide-ranging stress resistance relies on Lon protease, which is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance indicate surprising coordination between intracellular stress responses and suggest a novel hypothesis to explain high global mistranslation rates.

Klíčová slova:

Antibiotics – Cellular stress responses – DNA damage – DNA repair – Mutagenesis – Point mutation – Proteases – Transfer RNA


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